Biopolymers such as polyamino acids, polynucleic acids, polyphenols and polysaccharides have evolved over billions of years to carry out a myriad of tasks such as catalysis, molecular recognition or the storage of energy or information. Biopolymers are synthesized from a very limited number of building blocks and it is their complex three-dimensional structures that are responsible for their highly specialized properties. Polyamino acids and polynucleic acids are synthesized in template-directed catalyzed reactions yielding monodisperse linear polymers composed of a specific sequence of monomers; whereas polyphenols and polysaccharides are prepared via untemplated catalyzed reactions yielding polydisperse polymers with a wide variety of potential structures (including linear and branched) depending upon the monomers involved. Biopolymers are commonly occurring structural elements of biological systems. Polysaccharides are the most abundant biopolymers on earth, cellulose and chitin serve as structural elements in plant cell walls and animal exoskeletons; polyphenols such as lignins are important structural elements in wood and other plants; and polyamino acids such as collagen and elastin are the main components of blood vessels, connective tissues and skin in animals and humans.
Polyamino acids (known as polypeptides or proteins) in higher organisms are synthesized from combinations of up to 19 amino acid monomers (—NH—CHR1—CO—) and one imino acid monomer (—NR1—CHR2—CO—), linked via amide bonds (also known as peptide bonds) between the monomers (which are more commonly referred to as residues). In higher organisms, only the L-amino acids are used as monomers, whereas in lower life forms (such as bacteria or lower plants) D-amino acid monomers can also be incorporated. In vivo, polyamino acids are synthesized in a template-directed fashion: first, DNA is used as a template in the synthesis of messenger RNA (mRNA) via a process known as transcription; mRNA can subsequently be used as a template by ribosomes in the synthesis of a sequence-specific polypeptide, this process is known as translation, because the information stored in a polynucleic acid (genetic code) is translated into information in a polyamino acid (functional code).
The sequence of residues in a polypeptide is known as the primary structure. The amino acid residues display different functional groups on the polyamide backbone of the polymer; these functional groups can be categorized as polar, non-polar, aromatic, anionic or cationic. After polymer synthesis, supramolecular interactions (such as hydrogen bonding between the amide bonds in the backbone of the polymer, or π interactions between aromatic groups) determine the local conformation of the polypeptide which is known as the secondary structure—prominent examples of common secondary structures are: α-helices, β-sheets and β-turns. Hydrogen bonds between the hydrogen atom attached to the nitrogen atom of an amide and the carbonyl oxygen atom of the fourth amino acid on the amino-terminal side of the peptide bond encourage the polymer to coil around an axis into an α-helix; each helical twist contains on average 3.6 amino acids and is 5.4 Å in length. α-helix formation is encouraged by ion pair formation between oppositely charged residues 3 or 4 amino acids apart, and π-interactions between similarly spaced aromatic amino acids. Less common are helical twists containing 3 amino acids (known as 31- or 310-helices). In certain cases, hydrogen bonding between chains (intrachain or interchain) that are side by side cause the polypeptide chain to adopt a zigzag conformation, known as a β-sheet. Amino acids with small side chains such as glycine and alanine allow stacking of β-sheets, whereas bulkier amino acids discourage this sort of assembly process. Turns and loops are also frequently occurring secondary structures in polypeptides. Particularly common are 180° loops, known as β-turns, which consist of 4 amino acids where the carbonyl oxygen of the first amino acid is hydrogen bonded to the hydrogen on the amine of the fourth amino acid. Importantly, the second and third amino acids do not participate in hydrogen bonding.
Polypeptides therefore contain regions that are either locally disorganized or locally organized dependent upon their primary structure, and covalent or non-covalent cross links between different regions within a polypeptide chain determine the overall three-dimensional arrangement of the polypeptide chain, which is known as the tertiary structure. Further interactions (covalent or non-covalent) between individual polypeptide chains (identical or different) determine a protein's quaternary structure. The process by which polypeptides assume their secondary, tertiary and quaternary structures after polymerization is known as ‘folding’ and is in some cases aided by accessory proteins. Once the process of folding is complete and the polypeptides are fully assembled into their biologically active conformations, the polypeptides are said to be in their ‘native’ state.
As mentioned above, biopolymers based on polyamino acids such as collagen and elastin are a major component in nature, often displaying advantageous properties such as excellent tensile strength, extensibility and toughness that render them attractive for applications such as medical or cosmetic uses. However, despite the knowledge about such naturally occurring biopolymers and their properties, the provision of such compounds in amounts suitable for applications remains a challenge. Accordingly, there is still a need to provide such biopolymers yielding structures with advantageous properties such as e.g. excellent tensile strength, extensibility and toughness.
This need is addressed by the provision of the embodiments characterized in the claims.